Kidney fibrosis is a critical health problem in the United States because it represents the final common pathway of all chronic kidney diseases yet no biomarkers exist to aid in its diagnosis or measurement of progression. Using cutting edge genomic techniques, we have identified six novel biomarkers of kidney fibrosis and we hypothesize that levels of these biomarkers will accurately reflect kidney fibrosis in humans. In this proposal we have assembled three unique human patient cohorts in which to evaluate these six biomarkers, using histologic kidney fibrosis from kidney biopsy as the gold standard. We will measure biomarker levels in both serum and urine, using controlled and validated assays, and compare biomarker levels with the degree of tubulointerstitial fibrosis observed histologically. The most promising biomarkers will then be measured in a prospective chronic kidney disease cohort, comparing rapid progressors with those who do not progress. Our multidisciplinary team includes individuals with expertise in preclinical fibrosis models, assay development, molecular biology, regulatory compliance, clinical epidemiology, trial design and biostatistics. Together, the proposed experiments represent a rigorous evaluation of these six biomarkers in human chronic kidney disease and will pave the path forward for future studies that will transform clinical trial design and care in nephrology.